Treatment of Acute Ischaemic Stroke and Concomitant Multiple Arterial Splanchnic Thromboses in a Patient with Immune Thrombocytopenia on Thrombopoietin Agonist: A Case Report

Round 1

Reviewer 1 Report

Frol et al have reported a case of acute ischaemic stroke and multiple arterial splanchnic thromboses in a patient with immune thrombocytopenia on TPO agonist. The case is very interesting and is of enough scientific value to be presented to a broader readership. I recommend this case for publication.

Author Response

Dear reviewer.

Thank you very much for your response and comments.

As written there is no additional changes to be made.

Reviewer 2 Report

The manuscript entitled “Treatment of acute ischaemic stroke and concomitant multiple 3 arterial splanchnic thromboses in a patient with immune 4 thrombocytopenia on TPO agonist: A case report” presents a case report of thrombolysis in a patient with ITP.

The case report is interesting, presenting a rare case, and in the second part a summary of cases in literature is presented. I have only some minor comments:

·       Case report:

o   L 83: by NIHSS the ‘score’ is missing

o   I find it interesting, that this patient had anaphylaxis. What medication did the patient take besides eltrombopag and dexamethasone? There were some publications about allergic reactions, angiooedma in IVT treated patients, where the patients received ACE inhibitor:

Kilian Fröhlich, Kosmas Macha, Stefan T. Gerner, Tobias Bobinger, Manuel Schmidt, Arnd Dörfler, Max J. Hilz, Stefan Schwab, Frank Seifert, Bernd Kallmünzer and Klemens Winder https://doi.org/10.1161/STROKEAHA.119.025260Stroke. 2019;50:1682–168Angioedema in Stroke Patients With Thrombolysis

·       Literature summary should be separated in a new paragraph and title

·       Discussion: Ln 196-202: From the sentences it seems, that the authors would like to show correlation between anaphylaxis after IVT and ITP. Of course, this might be the case, but it should be presented in a more logical way, what arguments are for and against it. I think this part needs clarification. Besides the given reference maybe a more complex work-up of anaphylaxia after IVT could be also referred, of course any other as well.  e.g. Lerario MP, Grotta JC, Merkler AE, Omran SS, Chen ML, Parikh NS, Yaghi S, Murthy S, Navi BB, Kamel H. Association Between Intravenous Thrombolysis and Anaphylaxis Among Medicare Beneficiaries With Acute Ischemic Stroke. Stroke. 2019 Nov;50(11):3283-3285. doi: 10.1161/STROKEAHA.119.026861

Author Response

We would like to thank the reviewer for all the comments and remarks. We have done a revision of the manuscript taking into account all the requests/suggestions.

Point-by-point responses to the comments are as follows:

1. Case report: L 83: by NIHSS the ‘score’ is missing

Thank you very much for your remark. As requested, we have added the word score. (Case report – page 2, line 83)

2. I find it interesting, that this patient had anaphylaxis. What medication did the patient take besides eltrombopag and dexamethasone? There were some publications about allergic reactions, angioedema in IVT treated patients, where the patients received ACE inhibitor: Fröhlich K, Macha K, Gerner ST, Bobinger T, Schmidt M, Dörfler A, Hilz MJ, Schwab S, Seifert F, Kallmünzer B, Winder K. Angioedema in Stroke Patients With Thrombolysis. Stroke. 2019 Jul;50(7):1682-1687. doi: 10.1161/STROKEAHA.119.025260. Epub 2019 Jun 11. PMID: 31182002.

Thank you for your comment. Our patient did not take any additional medication beside eltrombopag and dexamethasone.

3. Literature summary should be separated in a new paragraph and title

Thank you for your remark. We have separated the literature summary in a new paragraph and titled it. (page 5)

4. Discussion: Ln 196-202: From the sentences it seems, that the authors would like to show correlation between anaphylaxis after IVT and ITP. Of course, this might be the case, but it should be presented in a more logical way, what arguments are for and against it. I think this part needs clarification. Besides the given reference maybe a more complex work-up of anaphylaxia after IVT could be also referred, of course any other as well. e.g. Lerario MP, Grotta JC, Merkler AE, Omran SS, Chen ML, Parikh NS, Yaghi S, Murthy S, Navi BB, Kamel H. Association Between Intravenous Thrombolysis and Anaphylaxis Among Medicare Beneficiaries With Acute Ischemic Stroke. Stroke. 2019 Nov;50(11):3283-3285. doi: 10.1161/STROKEAHA.119.026861. Epub 2019 Sep 13. PMID: 31514696; PMCID: PMC6863087

Thank you very much for your remark. We entirely agree with the reviewers’ comment and accordingly added a text “Anaphylactic reactions in patients with AIS are very rare, but patients who received IVT had an 8-fold higher risk of anaphylaxis than patients who did not receive IVT, with the absolute risk of anaphylaxis reaching 1 in 200 patients [36]. There appears to be an independent association between IVT and anaphylaxis in stroke patients. Because alteplase (tissue plasminogen activator) is an endogenous molecule, it is very unlikely to cause anaphylaxis; it is more plausible that anaphylaxis is a hypersensitivity reaction triggered by the release of vasoactive substances [36]. ITP as an autoimmune disease is not a known cofactor for anaphylactic reaction, but specific immunotherapy might be [37]. We speculate that the anaphylaxis in our case may be a hypersensitivity reaction to vasoactive substances, which might be exacerbated by immunotherapy for ITP.” (Discussion – page 6, lines 198-205 and page 7, lines 206-207)

Author Response File: Author Response.pdf